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A Dose Escalation Study of SHP2 Inhibitor in Patients With Solid Tumors Harboring KRAS of EGFR Mutations

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05163028
Recruitment Status : Recruiting
First Posted : December 20, 2021
Last Update Posted : June 16, 2022
Sponsor:
Information provided by (Responsible Party):
HUYABIO International, LLC.

Brief Summary:
A Phase 1 dose escalation study in patients with advanced solid tumors harboring KRAS or EGFR mutations to determine the maximum tolerated dose and recommended Phase II dose of HBI-2376 and characterize its pharmacokinetic profile.

Condition or disease Intervention/treatment Phase
Non Small Cell Lung Cancer Colorectal Cancer Pancreatic Cancer Solid Tumor Cancer Cancer of Pancreas Cancer of Colon Drug: HBI-2376 Phase 1

Detailed Description:

A Phase 1, Open-Label, Dose Escalation of HBI-2376 in Patients with Advanced Malignant Solid Tumors Harboring KRAS or EGFR Mutations. The primary and secondary objectives are:

  1. To determine the MTD and recommended Phase 2 dose (RP2D), of HBI-2376 as an oral monotherapy for advanced solid tumors harboring KRAS or EGFR mutations
  2. To characterize the PK of HBI-2376 in subjects with advanced malignant solid tumors harboring KRAS or EGFR mutations

HBI-2376 is a SHP2 Inhibitor and will be dosed once daily throughout the escalation and expansion phase. Up to 42 subjects will be enrolled sequentially into the 3+3 dose escalation and monitored throughout the study for safety and tolerability. The dose escalation phase will consist of 6 cohorts, with doses ranging from 6 to 40mg. Once the MTD of RP2D is established, additional 6 subjects will be enrolled into the expansion phase at that dose level.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description: 3+3 Dose Escalation Design with Expansion
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Open-Label, Dose Escalation of HBI-2376 in Patients With Advanced Malignant Solid Tumors Harboring KRAS or EGFR Mutations
Actual Study Start Date : December 13, 2021
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : December 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Dose Escalation and Expansion
HBI-2376 will be given orally in ascending doses (escalation cohort), until the maximum tolerated dose or recommended Phase 2 dose is reached. Up to 6 patients will then be enrolled in the expansion cohort at the recommended dose.
Drug: HBI-2376
SHP2 Inhibitor




Primary Outcome Measures :
  1. To determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D), of HBI-2376 as an oral monotherapy for advanced solid tumors harboring KRAS or EGFR mutations. [ Time Frame: Up to 36 months ]
    Safety endpoints: Incidence of dose-limiting toxicities (DLTs), adverse events (AEs), and serious adverse events (SAEs) overall, by severity, by relationship to HBI-2376, and those that led to discontinuation of HBI-2376


Secondary Outcome Measures :
  1. Pharmacokinetic variables including maximum plasma concentration (Cmax) [ Time Frame: Cycle 1 (28 days) ]
    Pharmacokinetic variables including maximum plasma concentration (Cmax)

  2. Pharmacokinetic variables including minimum plasma concentration (Cmin) [ Time Frame: Cycle 1 (28 days) ]
    Pharmacokinetic variables including minimum plasma concentration (Cmin)

  3. Pharmacokinetic variables including Area Under the Curve (AUC) [ Time Frame: Cycle 1 (28 days) ]
    Pharmacokinetic variables including Area Under the Curve (AUC)

  4. Pharmacokinetic variables including clearance [ Time Frame: Cycle 1 (28 days) ]
    Pharmacokinetic variables including clearance

  5. Pharmacokinetic variables including serum half-life [ Time Frame: Cycle 1 (28 days) ]
    Pharmacokinetic variables including serum half-life

  6. Pharmacokinetic variables including volume of distribution [ Time Frame: Cycle 1 (28 days) ]
    Pharmacokinetic variables including volume of distribution



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Male or female at least 18 years of age at the time of signing the ICF prior to initiation of any study specific activities/procedures
  • Advanced malignant solid tumors with KRAS or EGFR mutations diagnosed by histology or cytology
  • Relapsed or refractory to, or intolerant of, or refuse approved or standard of care established therapy known to provide clinical benefit for disease
  • At least 1 measurable target lesion that meets the definition of RECIST v1.1
  • ECOG Performance Status of 0 or 1
  • Demonstrate adequate organ function
  • Must be able to swallow oral medications and must not have gastrointestinal abnormalities that significantly affect drug absorption

Key Exclusion Criteria:

  • History of another concurrent malignancy within 3 years prior to study entry, unless the malignancy was treated with curative intent and the likelihood of relapse is <5% in 2 years Note: Subjects with a history of squamous or basal cell carcinoma of the skin or carcinoma in the situ of the cervix may be enrolled
  • Untreated or symptomatic central nervous system (CNS) metastases Note: Subjects with asymptomatic treated CNS metastases are eligible provided they have been clinically stable and not requiring steroids for at least 4 weeks
  • Clinically significant cardiovascular disease, including stroke or myocardial infarction within 6 months
  • Any unresolved Grade 2 or greater toxicity from previous anti-cancer therapy, except alopecia, within 4 weeks of first study treatment administration
  • Active autoimmune diseases or history of autoimmune diseases that may relapse
  • Pregnant or nursing
  • Prior treatment with any SHP2 inhibitors
  • Any condition that required systemic treatment with either corticosteroids (>10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤14 days before the first study treatment administration
  • Treatment with other investigational drugs/devices within 4 weeks prior to first study treatment administration

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05163028


Contacts
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Contact: John Ning, MD,PhD,FAIC 858-280-1866 jning@huyabio.com
Contact: Lalitha Aiyer, MD,MS,MBA,FAIHM,IFMCP 858-798-8800 laiyer@huyabio.com

Locations
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United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Susan Hmwe    626-218-4404    shmwe@coh.org   
Sub-Investigator: Ravi Salgia, MD         
California Cancer Associates for Research and Excellence, Inc. (cCare) Recruiting
Encinitas, California, United States, 92024
Contact: Christina Spencer    760-452-3909    cspencer@ccare.com   
Principal Investigator: Alberto Bessudo, MD         
Providence Medical Foundation Recruiting
Fullerton, California, United States, 92835
Contact: Noli Raz    717-446-5642    Noli.Raz@stjoe.org   
Principal Investigator: David J Park, MD         
California Cancer Associates for Research and Excellence, Inc. (cCare) Recruiting
San Marcos, California, United States, 92069
Contact: Christina Spencer    760-452-3909    cspencer@ccare.com   
Principal Investigator: Alberto Bessudo, MD         
Sarcoma Oncology Recruiting
Santa Monica, California, United States, 90403
Contact: Victoria S Chua-Alcala, MD, CLS    310-552-9999    vchua@sarcomaoncology.com   
Principal Investigator: Sant Chawla, MD         
UCLA Hematology/Oncology Recruiting
Santa Monica, California, United States, 90404
Contact: Joanna Gutierrez    310-633-8400 ext 16370    mailto:JGGutierrez@mednet.ucla.edu   
Principal Investigator: Jonathan Goldman, MD         
United States, Florida
Orlando Health, Inc. Recruiting
Orlando, Florida, United States, 32806
Contact: Kiera Grofsik    321-841-6626    kiera.grofsik@orlandohealth.com   
Principal Investigator: Sajeve Thomas, MD         
BRCR Medical Center Recruiting
Plantation, Florida, United States, 33322
Contact: Ines Padron    561-447-0614 ext 102    ipadron@brcrglobal.com   
Principal Investigator: Harshad Amin, MD         
United States, Ohio
Gabrail Cancer Center Recruiting
Canton, Ohio, United States, 44718
Contact: Kim Roby    330-492-3345 ext 227    kroby@gabrailcancercenter.com   
Principal Investigator: Nashat Gabrail, MD         
United States, Texas
Texas Oncology - Tyler Recruiting
Tyler, Texas, United States, 75702
Contact: Penny Watkins, RN    903-579-9800    penny.watkins@usoncology.com   
Principal Investigator: Donald A Richards, MD, PhD         
United States, Virginia
Virginia Cancer Specialists Recruiting
Fairfax, Virginia, United States, 22031
Contact: Cynthia DeLeon    210-580-9521    cdeleon@nextoncology.com   
Principal Investigator: Alexander Spira, MD, PhD         
Sponsors and Collaborators
HUYABIO International, LLC.
Investigators
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Principal Investigator: Ravi Salgia, MD City of Hope Comprehensive Cancer Center
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Responsible Party: HUYABIO International, LLC.
ClinicalTrials.gov Identifier: NCT05163028    
Other Study ID Numbers: HBI-2376-101
First Posted: December 20, 2021    Key Record Dates
Last Update Posted: June 16, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by HUYABIO International, LLC.:
KRAS
EGFR
SHP2
FIH
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Colonic Neoplasms
Neoplasms
Neoplasms by Site
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Endocrine Gland Neoplasms
Pancreatic Diseases
Endocrine System Diseases